Peripheral steroid sulfatase inhibition potentiates improvement of memory retention for hippocampally administered dehydroepiandrosterone sulfate but not pregnenolone sulfate.

Dehydroepiandrosterone sulfate (DHEAS) improves memory retention when administered peripherally. Estrone-3-O-sulfamate (EMATE), a steroid sulfatase inhibitor, potentiates the effect of DHEAS on memory retention such that lower doses of DHEAS improve memory retention. It is not clear if this effect is mediated by both compounds entering the central nervous system. In the current studies, mice were trained to avoid footshock in a T-maze and memory retention was tested 1 week later. DHEAS, injected into the hippocampus after training, improved memory retention in a dose-dependent manner. In previous studies, pregnenolone sulfate (PREGS) improved memory retention when injected into the hippocampus. EMATE, administered peripherally, potentiated the effect of centrally administered DHEAS on memory retention. However, EMATE did not potentiate the effect of centrally administered PREGS. It was concluded that EMATE, acting peripherally, increased plasma levels of DHEAS which entered the brain and added to the effect of centrally administered DHEAS. The failure of EMATE to potentiate PREGS is discussed.